A method for constructing multiple nucleic acid sequences for use as positive controls in a genetic test is described. Compositions according to the invention including multiple nucleic acid sequences constructed as described are the optimal controls for simultaneously testing multiple variable nucleic acid sequences at one or more DNA or RNA sites in a subject or subjects. Sequences according to the invention can be prepared chemically and/or by PCR amplification for use directly or after cloning and propagation. At the same time, some sequences can be PCR amplified and/or cloned directly from total genomic DNA obtained from an individual carrying the mutation or variant. Alternatively, the normal sequence to be changed can be cloned and then modified by site directed mutagenesis. Several single mutant or polymorphic sequences that together comprise a panel of multiple control sequences can be added individually to single site tests or mixed together or ligated together by further PCR or by cloning into vectors prior to use in individual or multiplex tests. Controls sequences constructed according to the invention can be used when testing any genetically transmitted nucleic acid sequence by organizations testing quality assurance and by companies maintaining quality control of manufactured genetic test kits.
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